Xanthine oxidoreductase activity correlates with vascular endothelial dysfunction in patients with type 1 diabetes

Acta Diabetol. 2020 Jan;57(1):31-39. doi: 10.1007/s00592-019-01362-1. Epub 2019 May 15.

Abstract

Aims: Xanthine oxidoreductase (XOR) is an enzyme regulating uric acid synthesis and generation of reactive oxygen species. Several studies suggested relationship between XOR and atherosclerotic diseases; however, few previous studies have directly examined the relationship between XOR and vascular endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between XOR activity and vascular endothelial function in patients with T1DM.

Methods: Seventy-one patients with T1DM participated in the study and underwent assessments, including plasma XOR activity and flow-mediated dilation (FMD), to measure vascular endothelial function.

Results: The natural logarithm value of XOR activity (ln-XOR) was 3.03 ± 0.99 pmol/h/mL, and FMD was 5.5% ± 2.4%. FMD was inversely and significantly correlated with ln-XOR (correlation coefficient: r = - 0.396, P < 0.001), UA (r = - 0.252, P = 0.034), and asymmetric dimethylarginine (ADMA) (r = - 0.414, P < 0.001). ln-XOR showed positive correlation with HbA1c (r = 0.292, P = 0.013), ALT (r = 0.658, P < 0.001), and ADMA (r = 0.363, P = 0.002). Stepwise multiple regression analysis showed that ln-XOR (standard partial regression coefficient: β = - 0.254, P = 0.018) was an independent explanatory variable of FMD.

Conclusions: The results of this study showed for the first time that XOR activity is associated with glycemic control in patients with T1DM and that XOR activity is associated with vascular endothelial dysfunction.

Keywords: Glycemic control; Type 1 diabetes; Vascular endothelial function; Xanthine oxidoreductase.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / enzymology*
  • Diabetes Mellitus, Type 1 / genetics
  • Endothelial Cells / enzymology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Xanthine Dehydrogenase / blood*
  • Xanthine Dehydrogenase / genetics

Substances

  • Biomarkers
  • Blood Glucose
  • Reactive Oxygen Species
  • Xanthine Dehydrogenase